National Center for Emerging and Zoonotic Infectious Diseases

Evidence to Recommendations Framework: Vaccination with JYNNEOS for Persons At Risk Advisory Committee on Immunization PracticesOctober 25, 2023Agam Rao, MDCAPT, US Public Health ServicePoxvirus and Rabies BranchCenters for Disease Control and Prevention
Evidence to Recommendations (EtR) Framew

 Structure to describe information considered in moving from 

ACIP vaccine recommendations

 Provides transparency around the impact of additional facto

deliberations when considering a recommendation
EtR question

Does ACIP recommend vaccination with the 2-dose* JYNNEOS vafor persons aged 18 years and older at risk† for mpox?

*Dose 2 administered 28 days after dose 1

†Persons at risk: • Gay, bisexual, and other men who have sex with men, transgender or nonbinary people wh

6 months have had one of the following:

• A new diagnosis of ≥ 1 sexually transmitted disease

• More than one sex partner • Sex at a commercial sex venue• Sex in association with a large public event in a geographic area where mpox transmis

occurring

• Sexual partners of persons with the risks described in above

• Persons who anticipate experiencing any of the above
Policy question: Should the 2 dose JYNNEOS vaccine series* be reco

for persons aged 18 years and older at risk

† for mpox

?

Population Persons aged 18 years and older at risk for mpoxIntervention Vaccination with JYNNEOS®Comparison No vaccinationOutcome

a) Prevention of disease

b) Severity of diseasec) Serious adverse eventsd) Myo-/ peri- carditis 

*Dose 2 administered 28 days after dose 1†Persons at risk: • Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had one of the following:

• A new diagnosis of ≥ 1 sexually transmitted disease• More than one sex partner • Sex at a commercial sex venue• Sex in association with a large public event in a geographic area where mpox transmission is occurring

• Sexual partners of persons with the risks described in above

• Persons who anticipate experiencing any of the above
EtR Domains

EtR Domain Question(s)Public Health Problem • Is the problem of public health importance?

Benefits and Harms • How substantial are the desirable anticipated effects?

• How substantial are the undesirable anticipated effects?

• Do the desirable effects outweigh the undesirable effects?

Values • Does the target population feel the desirable effects are large relative 

effects?

• Is there important variability in how patients value the outcome?

Acceptability • Is the intervention acceptable to key stakeholders?

Equity • What would be the impact of the intervention on health equity?

Feasibility • Is the intervention feasible to implement?

Resource Use • Is the intervention a reasonable and efficient allocation of resources?
Public Health Problem
Are continued mpox cases of public health 

importance? >1.25 million doses of JYNNEOS have been administered in th However, national vaccine coverage remains lower than idea

because of lower perceived risk in the last 6 months

 Mpox cases continue to occur domestically and internationa

clusters

 Modeling data suggests larger outbreaks may occur if vaccine 

remains <50% nationally for persons at risk of mpox

 Severe disease and deaths continue to occur
Benefits and Harms
Main source of VE data has been three U.S. s

 CDC EPIC study CDC Multi-jurisdictional study New York State study Estimated VE for preventing mpox disease ha

from 66-89% for the 2-dose vaccine series
Multi-jurisdictional study: estimate of VE for 

preventing infections among immunocompetself-reported immunocompromised persons

*Adjusted for age, race/ethnicity, immunocompromised status, reported close contact with a confirmed/suspected mpox case in 3 weeks prior to index event• Only recently able to evaluate VE of self-reported immunocompromised, confidence interval is s• Modifications in protocol needed to evaluate VE for objectively confirmed immunocompromised 
How substantial are desirable anticipated eff

JYNNEOS?

 ACIP previously recommended use of JYNNEOS 

– Persons at increased risk of occupational exposure to orthopox– Persons at-risk for mpox during mpox outbreaks

 Subsequent data has supported its effectiveness for the pop

impacted by the ongoing outbreak
How substantial are desirable anticipated eff

JYNNEOS?

 ACIP previously recommended use of JYNNEOS 

– Persons at increased risk of occupational exposure to orthopox– Persons at-risk for mpox during mpox outbreaks

 No new safety signals identified from pre-licensure studies The adverse events most commonly reported to VAERS ha

injection site symptoms (redness, swelling, pain, itching)
Balance between desirable effects relative to 

undesirable effects of JYNNEOS

 Desirable anticipated effects considered large Undesirable anticipated effects considered small

Do the desirable effects outweigh the undesirable effects?

Favors intervention Favors comparison Favors both Favors neit
EtR Domain: Values
Early in outbreak response: National surveys 

strong interest in vaccine During Aug-Nov 2022, >85% of respondents in the American 

Transformative HIV Study (AMETHST) were interested in vaccuptake doubled from August to September

 During August-Dec 2022, 50% of Porter-Novelli survey respo

identified as LGBTQ+ felt the vaccination is important to prot

 During Oct-Nov 2022, >70% of MSM in a San Francisco surve

experiencing homelessness reported that they would accept accepted vaccination

 During October-December 2022, an American Men’s Interest 

(AMIS) showed that those who were concerned about mpox more likely to be vaccinated

https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-21-018.htmlhttps://emoryamis.org/wp-content/uploads/2022/08/2022-Monkeypox-Survey.pdfhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htmFilardo TD. Vaccine. 2023 Sep 7;41(39):5673-5677. 
Early in outbreak: Persons seeking vaccinatio

as expected, supportive of the JYNNEOS vacc DC PEP ++ Study: CDC and DC Health collaboration to follow 

persons at elevated risk of mpox exposure in Washington D.Cpresented for JYNNEOS vaccination, Aug 2022-Oct 2022

– Survey with 866 adults – >85% agreed or strongly agreed that vaccines for mpox should 

anyone who wants the vaccine

– 82% were likely or very likely to get a third dose if it was recom

 Qualitative interviews August and September 2022 among a

presenting for JYNNEOS vaccine in Washington DC

– Many participants grateful that LGBTQ+ were given priority vac

(suggests interest in vaccine)

Hassan, R. (in press). Sexually Transmitted Diseases
Early in outbreak: Studies indicated conflictin

about receiving JYNNEOS vaccines Curtis et al. Survey with 320 persons, primarily MSM living in 

risk for mpox. September 2022

– 24.1% received 2 vaccine doses, 27.5% received one dose, 47.5– Persons who were vaccinated were more likely to have higher e

someone with mpox, express concern about their safety, and lereport recent food insecurity

 Turpin et al. Qualitative interviews with 24 Black MSM attend

prevention-related events in greater D.C. area, May 2022

– Lack of availability of mpox vaccines was common concern sugg– Vaccine hesitancy was also common

https://pubmed.ncbi.nlm.nih.gov/37236817/https://pubmed.ncbi.nlm.nih.gov/37510557/
More recent: State of vaccine confidence rep

2023 Review of mpox-related discussions on 23 news and 

social media outlets in the Chicago area during themonth following the CDPH media release indicating an increase in mpox cases, particularly among previously vaccinated persons

 Findings: 

– Mpox vaccine hesitancy among general public and LGBTQaffiliated groups noted– Questions raised

• Effectiveness and safety of the vaccine (e.g., sentiment expressed 

that vaccine is experimental)

• Distrust in reporting (e.g., Suspicion that mpox reporting is 

exaggerated)

https://www.cdc.gov/vaccines/covid-19/downloads/SoVC-MPOX-062723.pdf
More recent: Interviews with 18 patients ass

with mpox cluster in Chicago, May 2023 Fully vaccinated, partially vaccinated, unvaccinated interview Most stated they would recommend vaccine to others Most vaccinated persons felt vaccine was effective in reducin Some assumed it would prevent infection Unvaccinated reported initial interest in vaccine when supply 

and they were unable to receive it; they reported they did nobecause case counts decreased so they assumed diminished 
More recent: Online focus group used by CDC 

develop communication material, July 12, 20 Session conducted with 52 persons

– Participant inclusion criteria:

• Identify as men (including transgender men and transgender women)• Unvaccinated for mpox and never diagnosed with mpox• 18-45 years of age• Sex with 2 or more men within past 6 months

– Participant demographics: average age 30-34 years; 48% Black, 37% W

Hispanic/Latino; 75% gay, 21% bisexual

 Exposure to communication materials increased interest in receivin

– Information about mpox vaccine safety, effectiveness, and current th

affected interest

– Current risk of mpox and protecting community were motivating

 Some people did not change their minds
Target population sentiments

 Vaccine demand was high early in the outbreak response National surveys with the affected population indicate overall 

JYNNEOS vaccinations
Target population sentiments

 Interest and intent to get vaccinated varies among the affecte Lower perceived risk of mpox may contribute to reduced inter

later in the outbreak 
EtR Domain: Acceptability
Stakeholder perceptions: Health departmen

 Health departments requested JYNNEOS and organized vacci

campaigns

https://aspr.hhs.gov/SNS/Pages/JYN
Stakeholder perceptions: Sermo survey of cl

 Sermo*: Online community of >1.3 million 

clinicians

 July 31 - August 1, 2022 survey results of U.S. 

clinicians (n=415): 69% felt U.S. without enough mpox vaccine to handle outbreak

 September 12, 2022 survey of U.S. clinicians 

(n=62)

• 66% had treated at least one mpox patient• 76% knew where a patient could get 

JYNNEOS vaccination

• 86% wanted to be able to provide 

vaccination in their office

*https://app.serm
Porter-Novelli Survey of Pediatricians (n=102

Family Practice (FP) Practitioners (n=104) Added 3 mpox vaccine questions to survey on pediatric COVI

attitudes and behaviors

 Description of respondents' clinical practices:

– 85% of FP and 88% of Pediatricians cared for children 12-– 70% of FP and 60% of Pediatricians cared for patients 18+ – Majority (75%) in private practice; 14% practiced in FQHC– 54% had >1500 patients in their practice
Porter Novelli Survey: Preference to provide JYNNEOS within m

PN survey of Pediatricians (N=102) and Family Practitioners (

2023
Shift in vaccine administration sites from pub

clinics to medical centers

• Public health providers a

vaccines through Mar 20

• Medical care providers a

increasing proportion of of the outbreak

• Pharmacies consistently 

vaccines

Public Health 

Provider or

Clinic

Medical

Center

Provider

Commercial 

Vaccination 

Service

Provider

Pharmacy Other

Percentage of Doses Administered
Categories of medical providers administering 

From 2022 to 2023, there wsignificant increases in vacc• Primary care offices• Federally qualifying heal• Other health centers

Primary 

Care

Hospital FQHC Health 

Center -

Other

Health 

Center -

STD/HIV

Percentage of Doses Administered

FQHC: Federally qualifying health center
Online focus group by CDC: Healthcare provid

perceptions of sexual health and mpox Conducted to explore provider knowledge, attitudes, and practices 

service delivery, including those specific to mpox

 Recruitment targeting 50 providers via external recruiting firm 41 total participants – diverse by gender, race/ethnicity, practice set

methods for patients (e.g., private insurance plans, Medicaid, Medigovernment programs), and clinical profession

 61% reported spending ≥60% of their time providing sexual health s 59% private healthcare setting, 29% private and publicly funded, 10

funded

 54% in private practice, 20% STD/HIV/family planning clinic, 10% FQ

or urgent care
Responses from healthcare provider participa

 68% had never managed an mpox case 34% believe mpox is a threat to public health 32% reported mpox is important to their patient populations 51% believe that mpox services (e.g., counseling) should be i

standard care for the following reasons

– Increase access to vaccine– Improve education and awareness for patients– Ensure STI screening is comprehensive
Is the intervention acceptable to key stakeho

Is the intervention acceptable to key stakeholders

No Probably no Uncertain Probably yes Yes Va

 Health departments and clinicians are supportive of mpox va

pediatricians would prefer to refer patients to other clinics to JYNNEOS

 Family practitioners would like to be able to provide JYNNEOS 

clinics

 There has been a shift from JYNNEOS provided by public hea

JYNNEOS provided by medical center providers, including STI 
EtR Domain: Resource Use
Is the intervention a reasonable and efficient 

allocation of resources

 Current resources

– Vaccine only available via national government stockpiles– JYNNEOS stockpiled for smallpox preparedness– Doses used need to be replenished – Significant use of resources (e.g., shipments, transportation, pe

the outbreak and routine recommendation could be further dr

 Potential resources in the future: Uncertain whether it will b

commercialized but if so, unknown costs associated with com
EtR Domain: Equity
Mpox and health equity

 Disproportionate impact of mpox

– Gay, bisexual, and other MSM – Black and Hispanic persons– Persons experiencing homelessness

 Any vaccine administered may decrease the disparity betwee

population and others
Impact on health equity

 Will facilitate 1:1 counseling and information sharing in th

clinic; vaccine recommendation from a clinician is associatincreased vaccine uptake

 $5,000,000 allocated to community-based organizations (CBO

September 2023 to advance mpox prevention and vaccinatio

– CBOS essential to increasing vaccination coverage among those 

and provided pivotal role during 2022

– 42 CBOs funded so far

 If commercialized, there may be an impact on primary sites o

and on health departments

 Recommendation might facilitate broad acceptance of vaccination (

insurance companies, patients) because endorsed by ACIP after rigo

*https://www.cdcfoundation.org/pr/2023/mpox-vaccination-CBO-outreach
What would be the impact on health equity

What would be the impact on health equity?

Reduced Probably Reduced Probably no impact Pro

Increased Varies Don’t know

 Access to vaccine (vs. no vaccine) may improve the health of 

are at risk for mpox

 Routine recommendation may facilitate vaccinations
EtR Domain: Feasibility
Access to JYNNEOS vaccination if ACIP recom

 Continue via national stockpiles free of cost to patients and p Mpox provider agreements* do not have a termination date; 

continue as long as vaccine is acquired via the US governmencan include new providers

 Funding† provided to CBOs may improve feasibility If commercialized

§

– Via Medicare, Medicaid, commercial plans without copay– Uninsured children via Vaccines for Children Program– Some uninsured and underinsured adults might have diff

*https://www.cdc.gov/poxvirus/mpox/clinicians/provider-agreement.html† https://www.cdcfoundation.org/pr/2023/mpox-vaccination-CBO-outreach

§Uncertain whether it will be commercialized
Is the intervention feasible to implement?

Is the intervention feasible to implement

No Probably no Uncertain Probably yes Yes V

 Subcutaneous vaccine; easy to administer Standing orders available; JYNNEOS can be stored refrigerated for 8  Recent analysis of shift in vaccine providers demonstrates the cont

successful integration of JYNNEOS into providers’ practices (e.g., STsettings, HIV care pharmacies, LGBTQ+ affirming primary care practices)

 STI, HIV, and most family medicine/internal medicine providers com

providing vaccines but some pediatricians may prefer referring paticlinics

 If commercialized, similar to other vaccines, cost of vaccine might i

some populations
Summary of EtR

Domains Domains DoBenefits: How substantial are the desired anticipated effects

Large Values: Does the 

target population feel desirable effects are large

Probably Yes Impa

healtequit

Harms: How substantial are undesirable anticipated effects?

Small Is there important 

uncertainty about or variability in values?

Possibly important uncertainty or variability

Feasiimple?

Benefit / Harm: Favors 

intervention

Acceptable to stakeholders?

Yes Balan

Reasonable and efficient allocation of resources?

Uncertain
Balance of Consequences

Undesirable Undesirable Balance 

consequences clearly consequences probably desirable outweigh desirable outweigh desirable consequeconsequences in most consequences in most balanced osettings settingsDesirable consequences Desirable consequences There is inprobably outweigh clearly outweigh to determundesirable consequences undesirable consequences consequein most settings in most settings

X
Proposed recommendation

ACIP recommends vaccination* with the 2-dose

† JYNNEOS vaccin

persons aged 18 years and older at risk for mpox

§?

*Interim recommendation that ACIP will revisit in 2-3 years† Dose 2 administered 28 days after dose 1§Persons at risk: • Gay, bisexual, and other men who have sex with men, transgender or nonbinary people wh

6 months have had one of the following:

• A new diagnosis of ≥ 1 sexually transmitted disease

• More than one sex partner • Sex at a commercial sex venue• Sex in association with a large public event in a geographic area where mpox transmis

occurring

• Sexual partners of persons with the risks described in above

• Persons who anticipate experiencing any of the abov

e
For more information, contact CDC

1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.govThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

National Center for Emerging and Zoonotic Infectious DiseasesDivision of High-Consequence Pathogens and Pathology

Questions?